Fibrinolysis Flashcards
what is fibrinolysis dependent on?
Plasminogen (zymogen inactive precursor
What domains does plasminogen have an affinity for?
Kringle domains on cell surface & clot
What 2 things can activate plasminogen?
tPA
urokinase
What is the activated form of plasminogen called?
plasmin
Where is tPA and urokinases released from?
Damaged ECs
What inhibits conversion of plasminogen to plasmin?
PAI (derived from platelets)
What factors from coagulation also promote fibrinolysis?
Factor XIa
Factor XIIa
Kallikrein
What are the main fibrin breakdown products?
D-dimers
E-fragments
What is used to measure D-dimer content in blood?
Specific antibodies against D-dimers
What 2 diseases are associated with high levels of D-dimers?
DVT
pulmonary embolism
What organ produces plasminogen/
Liver
What are 3 other anti-fibrinolytic agents?
alpha 2 antiplasmin
alpha 2 macroglobulin
thrombin
What activates tPA?
Binding to fibrin (localised activation)
What does partial fibrin degradation causes?
Exposes further tPA binding sites -> positive feedback loop
What are tPA and uPA?
Serine proteases that cleave plasminogen
What are PAIs?
Serine protease inhibitors (serpins) that reduce tPA & uPA
What is tPA in an inactive complex with?
PAI-1
where is alpha2-antiplasmin synthesized?
Liver
What incorporates alpha2AP into the clot?
factor XIII
What happens if alpha2AP is incorporated into the clot?
Prevents & delays degradation of fibrin clot (permits vessel repair processes)
What are 3 commonly used thrombolytics?
Streptokinase
urokinase
recombinant tissue plasminogen activators
What are 4 disease where thrombolysis is used?
Myocardial infarction
stroke
massive pulmonary embolism
acute limb ischaemia
What are 4 types of acquired hyperfibrinolysis?
metabolic syndrome (elevated PAI)
trauma/surgery
inflammation
treated with anti-fibrinolytis
